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These functions are considered to act dualistically as preventing or facilitating cancer. This study aimed to clarify the expression and role of SIRT1 in endonnetrial carcinoma. Because a high-calorie diet was a well-known risk factor for endometrial carcinoma, we first hypothesized that SIRT1 might be downregulated in normal endometrial glandular cells of obese women. However, no correlation was observed between the expression of SIRT1 and body mass index (BMI). In contrast, regardless of BMI, the immunohistochemical expression of SIRT1 was significantly higher in endometrial carcinoma (108 cases) than in normal endonnetria (60 cases) (P\u003c0.05), and its overexpression was associated with a shorter survival (P\u003c0.05). Our experiments in vivo revealed that SIRT1 accelerated the proliferation of endometrial carcinoma cell lines (HHUA, HEC151, and HEC1B). SIRT1 overexpression significantly enhanced the resistance for cisplatin and paclitaxel in HHUA cells. Although p53 is an important target protein for SIRT1, the selective SIRT1 inhibitor (EX527) significantly suppressed the proliferation and cisplatin resistance of three endonnetrial carcinoma cell lines regardless of the p53 mutation status. In addition, SIRT1 overexpression in HHUA cells accelerated tumor growth and cisplatin resistance in nude mice, and EX527 significantly suppressed the growth of tumors of HHUA and HEC1B cells. No adverse effect of EX527 was observed in these mice. 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  1. 050 医学部, 大学院医学系研究科
  2. 0507 学位論文
  3. 博士(医学)

Sirtuin 1 promotes the growth and cisplatin resistance of endometrial carcinoma cells: a novel therapeutic target(Sirtuin1は子宮内膜癌細胞の増殖とシスプラチン耐性を亢進させる:新規治療標的の可能性)

http://hdl.handle.net/10091/00019756
http://hdl.handle.net/10091/00019756
704de447-4c14-4218-a0cf-69fa00af19fd
名前 / ファイル ライセンス アクション
15MR0009_shinsa.pdf 内容の要旨 (99.0 kB)
15MR0009_yoshi.pdf 審査結果の要旨 (118.0 kB)
15MR0009_ronbun.pdf 博士論文の全文 (3.1 MB)
Item type 学位論文 / Thesis or Dissertation(1)
公開日 2017-06-06
タイトル
言語 en
タイトル Sirtuin 1 promotes the growth and cisplatin resistance of endometrial carcinoma cells: a novel therapeutic target(Sirtuin1は子宮内膜癌細胞の増殖とシスプラチン耐性を亢進させる:新規治療標的の可能性)
言語
言語 eng
資源タイプ
資源 http://purl.org/coar/resource_type/c_db06
タイプ doctoral thesis
著者 浅香, 亮一

× 浅香, 亮一

WEKO 103728

浅香, 亮一

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出版者
出版者 信州大学
引用
内容記述タイプ Other
内容記述 浅香 亮一. Sirtuin 1 promotes the growth and cisplatin resistance of endometrial carcinoma cells: a novel therapeutic target(Sirtuin1は子宮内膜癌細胞の増殖とシスプラチン耐性を亢進させる:新規治療標的の可能性). 信州大学, 2016, 博士論文.
書誌情報
発行日 2016-06-08
学位授与番号
学位授与番号 13601乙第1194号
学位授与年月日
学位授与年月日 2016-06-08
学位名
学位名 博士(医学)
学位授与機関
学位授与機関名 信州大学(Shinshu university)
学位の区分
Doctoral
学位の分野
医学
学位の報告番号
乙第1194号
内容記述
内容記述タイプ Other
内容記述 雑誌に発表。LABORATORY INVESTIGATION. 95(12):1363-1373 (2015); doi:10.1038/labinvest.2015.119.
資源タイプ(コンテンツの種類)
内容記述タイプ Other
内容記述 Thesis
PubMed
識別子タイプ PMID
関連識別子 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=pubmed&term=26367491
関連名称 26367491
DOI
識別子タイプ DOI
関連識別子 https://doi.org/10.1038/labinvest.2015.119
関連名称 10.1038/labinvest.2015.119
出版タイプ
出版タイプ NA
出版タイプResource http://purl.org/coar/version/c_be7fb7dd8ff6fe43
WoS
Web of Science
URL http://gateway.isiknowledge.com/gateway/Gateway.cgi?&GWVersion=2&SrcAuth=ShinshuUniv&SrcApp=ShinshuUniv&DestLinkType=FullRecord&DestApp=WOS&KeyUT=000365458100003
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